Δρ. Στρουμπούλη Ιωάννη, Αναπληρωτή Καθηγητή Έρευνας, Ινστιτούτο Μοριακής Ογκολογίας που παρουσιάστηκε στην εκδήλωση "Life Sciences Business Day", Electra Palace Hotel, Αθήνα, 16/10/2008 (Hellenic Bio Cluster).

1. Biomedical Sciences Research Center “Alexander Fleming”
Fleming”
Greek Life Sciences Business Day, October 16 2008
Day,
John Strouboulis, PhD
Strouboulis,

2. Who we are
• Fleming Started its activities in 1998 as a Private Legal Entity
• Supervised by the GSRT, Greek Ministry of Development

3. Who we are
• Four Research Institutes currently active
• Immunology
• Molecular Biology and Genetics
• Molecular Oncology
• Cell and Developmental Biology
• (Microbiology and Virology)
• Scientific personnel-our most important asset
• 14 group leaders, more than 130 research
staff (staff scientists, grad students,
technicians, postdocs)
• Young scientists, international experience,
high caliber

4. What we do
• Institute of Immunology
– Pathogenesis of inflammatory pathways (Kollias, Aidinis, Graf, Douni,
Mosialos)
– Posttranscriptional gene regulation in inflammation and cancer
(Kontoyiannis)
– Angiogenesis (Kostourou)
• Institute of Molecular Biology and Genetics
– Epigenetic mechanisms of gene regulation in physiology and cancer
(Talianidis, Agalioti)
– Neuronal stem cells (Remboutsika)
– Neurobiology of learning and memory, neurodegeneration (Skoulakis)
• Institute of Molecular Oncology
– Signaling pathways in cancer (Panayotou)
– Hematopoiesis and leukemia (Strouboulis)
– microRNA bioinformatics (Hatzigeorgiou)

5. How we do it: Technology Platforms
Functional Functional
Genetics Genomics
Transgenesis Bioinformatics
Mutagenesis Phenomics
Animal
Biochemistry models Imaging
Molecular Proteomics
Cellular Genomics
Genetics

6. Our Achievements
• Achievements/Awards
– National and International Awards for researchers (Bodosakis’
Foundation, EMBO, Leukemia and Lymphoma Society)
– High Impact Scientific Publications
– Awards of competitive national and international grants
– Coordinator of an EU FP6 ‘Network of Excellence’ NoE in
Functional Genomics, €11m, 2005-2009
– Coordinator of an FP7 Marie Curie Initial Training Network on
Gene Regulation, €2.3m, 2008-2012
– 2002 and 2005: Centre of Excellence by international review
committee under the auspices of the Ministry of Development

7. Our Funding
6
projected
5
4
Funding
3
(million euros)
2
1
0
1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008
Year

8. Our Funding
Other income
1,20%
Services
Services Govt. subsidy Company contracts 1,50% Govt. subsidy
6,50% 15% 2,50% 17,50%
Company contracts 9%
EU grants 28,30%
31%
37% 50%
EU grants
National grants National grants
2005 2008
Total: € 4.4m Total: € 5.4m* * projected

9. Our Products and Services
– Proprietary animal models for human disease, e.g.
inflammatory, neurodegerenative diseases.
Preclinical drug testing and validation
– Cutting edge technical services and facilities built on
needs, capacities and expertise of Fleming’s
researchers. Available to external users as services
– Valorization
• Building intellectual property portfolios
• Spin off companies

10. Animal models of human disease:
inflammatory disorders
Joint Small intestine
Normal
Disease
Transgenic mice pathogenesis
or
Knockout mice
TNF pathway Inflammation
Rheumatoid Arthritis Crohn’s disease
• Understanding pathogenesis • Preclinical drug evaluation
• New therapeutic and
diagnostic target identification
George Kollias group (RA, Crohn’s, EAE etc.)

11. Animal models of inflammatory disease:
preclinical evaluation contracts
Contracts with:
250
• Centocor
• Isis Pharma
200 • BASF
• Amgen
• Merck
150
Revenue
• Medidom
(x1000 €) • Abbott
100 • Novo Nordisk
• Celltech
50
• Millenium Pharma
• Domantis
• Peptech
0
2000 2001 2002 2003 2004 2005 2006
• Ablynx
• Direvo
Year
• Debiopharm
• Abgenix
Fleming’s first spin-out company • Chemocentryx

12. Company Profile
Founded: last quarter of 2006 as a spin off company of BSRC Al. Fleming.
Services: Pre-clinical drug evaluation models and services using transgenic mice
Humanized transgenic models of autoimmune and inflammatory conditions (arthritis,
cachexia, sepsis, multiple organ failure, inflammatory bowel disease)
Induced models (CIA, EAE, sepsis etc)
Gene expression profiling
Customized protocols
Histopathology
Mouse Models: proprietary, world recognized for human disease, FDA recommended.
Facilities: independent laboratories/offices
R&D: Active
generates new and novel humanized mouse models.
Participates in FP6 and FP7 European grants
Staff: Six well trained and experienced scientific personnel
Clients: Big Pharma, Biotechnology companies (Europe, USA, Australia)

13. Animal models of human disease:
Alzheimers in Drosophila
30
25
20
Revenue
(x1000 €) 15
10
5
normal
0
2004 2005 2006
EnVivo Pharma
Fly school: Μemory and learning,
lesions
enhancing compounds?
30 day old aged fly
Makis Skoulakis group

14. Fleming Service Units and Facilities
• Protein Chemistry Lab, ISO Certified
• Animal House, ISO Certified
• Transgenic Facility, ISO Certified
• Genotyping Facility
• Expression Profiling Facility and BioIT Unit
• Flow Cytometry Facility
• Innovation and Enterprise Unit

15. Protein Chemistry Lab
Cutting edge services in biomolecular
and protein interaction characterization
Protein identification by mass spectrometry
Mapping of protein post-translational modifications
Protein expression, purification and characterization
Protein fractionation by various electrophoretic methods
2D protein electrophoresis
BIACORE Peptide fractionation by high pressure chromatography
Analysis of biomolecular interactions by biosensors
Analyte identification in clinical samples
Protein and nucleic acid quantitative analysis
Mass spectrometry
FPLC
Head: Dr. George Panayotou
EN ISO 9001:2000 Certification
HPLC

16. Protein Chemistry Lab
National Cancer Institute
McGill University
100
University College London
90 Wyeth Hellas
80 Schering-Plough
70
Aristotelian University, Thessaloniki
Revenue Ludwig Institute for Cancer Research
(x1000 €) 60 Hellenic Pasteur Institute
50 BioCryst Inc.
40 Athens University Medical School
Kimmel Cancer Center
30
University of Ioannia
20
National Metsovion Technical University
10 Agios Savvas Hospital
0 University of Thessaly
2002 2003 2004 2005 2006 2007 2008 Dimokritos Research Center
Erasmus University
Patras University
Head: Dr. George Panayotou

17. Animal House
• Biggest facility in Greece
– 600m 2, capacity for 18,000
mice
– 8 caretakers, 2 technicians, 2
senior scientists
– EN ISO 9001.2000
certification
• Services
– Breeding, hosting and supply
of mouse strains, wild type
and transgenic
– Handling of mice, surgical
procedures, sample taking
– γ irradiation for bone marrow
transplantation
– Histology lab
– Internal and external users
Head: Dr. Marie Kamber

18. Laboratory Animal Science Course

19. Genotyping Facility
Clinical diagnostics
• Mutation screening
• Customized
mutation screening
assays
• Pharmacogenetics
• CpG methylation
status quantification
• Microbial / viral
detection and
resistance
assessment
Head: Dr. Eleni Douni
Pyrosequencing

20. Expression Profiling Facility and BioIT
Unit
• Affymetrix platform for
RNA expression analysis,
e.g. clinical samples
• Illuminex platform for
multiplex analysis of
several markers
• Bioinformatic analysis
and support, data mining
Head: Dr. Vasilis Aidinis

21. The future
• Participation in European Research
Infrastructures, e.g. Infrafrontier
• Implementation of the entire drug
discovery and development process
• Business development through IP
portfolios, spin off companies
• Biotechnopolis

22. Infrafrontier
The European Infrastructure for
phenotyping, archiving and dissemination
of disease (mouse) models
• Germany: GSF; HZI
• UK: MRC/MGU, Welcome Trust Sanger; EBI
• France: ICS, CDTA/CDTA
• Italy: CNR; Government
• Sweden: Karolinska
• Spain: Univ. Barcelona; Madrid
• Portugal: Gulbenkian Institute
• Greece: Fleming Center
• Finland: Biocenter Oulu

23. The Biomedical and Life Sciences Infrastructure
Landscape

24. Drug Discovery Process
Preclinical
In vivo Tests
Target Clinical Trials Pharmacology
Identification
ADMET profiles
Lead Optimization
Signal 2: ATP [%]
Genomics
Frequency
Chemoinformatics
> 300% Hits
Proteomics
UnspezifischCompound
Häufigkeit
oder toxisch Control
Target < 60 %
Validation SignalLigand
1: [%]
Functional Data Mining
Assay Development
Genomics – Virtual Screening
Animal models Lead Identification

25. The future
• Participation in European Research
Infrastructures, e.g. Infrafrontier
• Implementation of the entire drug
discovery and development process
• Business development through IP
portfolios, spin-out companies
• Biotechnopolis

26. Innovation & Enterprise Unit
• Formerly Technology Transfer Office
• Established in 2005 with GSRT Grant
– Now funded directly via Fleming
• Responsible for:
– Management of Fleming IP
– Business Development Activities for Fleming IP
– Negotiation of R&D contracts
• Material Transfer Agreements
• Contract Research
• Collaborative Research
• Service Agreements etc
• More than 300 agreements managed in the last 3 years

27. Innovation & Enterprise Unit
Achievements
• Patent portfolio around 2 technologies
– License for one patent under negotiation
– Other patent applications under consideration
• Supported establishment of BioMedCode,
Fleming’s first spin-out company
• Established working relationship with several big
pharmas via major Biotech conference
– Negotiating collaborative deals now!
– Maintain contact with others for the future…

28. THE ALEXANDER FLEMING BIOTECHNOPOLIS
Research Institutes
Mouse clinic
Technology park
• Second building for Fleming’s Research Institutes, Facilities and
European Research Infrastructures
• New research centers with complementary research activities
• Biobusiness park, incubator space, tech transfer services
• Science in Society Cultural Center, housing the Alexander Fleming
Museum, Science Sculpture Park, Conference Center facilities